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Biomedical subjects

M Tu

Publications and source records attributed to M Tu.

At least 19 recordsLinked to original sources

Precipitation variability in the Meuse basin in relation to atmospheric circulation.

The distribution of precipitation events in the Meuse basin during the past century has been found to reflect the large-scale atmospheric circulation, as characterised by the Grosswetterlagen system. Statistical analysis of the long observation records (1911-2002) for the basin showed that although the annual (November to October) and winter half-year (November to April) frequencies of wet days > or = 1 mm/day) were nearly stable, the associated precipitation amounts have significantly increased since 1980. From 1980 onwards, the very wet days (> or = 10 mm/day) in the winter half-year have become more frequent. No obvious change was identified for the summer half-year (May to October) very wet days. Both the precipitation amounts of wet and very wet days in the winter half-year and the occurrence of associated atmospheric circulation of the types/sub-types west cyclone, southwest cyclone and northwest cyclone showed a significant increase around 1980.

Air Movements↗

An integrated "4-phase" approach for setting endocrine disruption screening priorities--phase I and II predictions of estrogen receptor binding affinity.

Recent legislation mandates the US Environmental Protection Agency (EPA) to develop a screening and testing program for potential endocrine disrupting chemicals (EDCs), of which xenoestrogens figure prominently. Under the legislation, a large number of chemicals will undergo various in vitro and in vivo assays for their potential estrogenicity, as well as other hormonal activities. There is a crucial need for priority setting before this strategy can be effectively implemented. Here we report an integrated computational approach to priority setting using estrogen receptor (ER) binding as an example. This approach rationally integrates different predictive computational models into a "Four-Phase" scheme so that it can effectively identify potential estrogenic EDCs based on their predicted ER relative binding affinity (RBA). The system has been validated using an in-house ER binding assay dataset for 232 chemicals that was designed to have both broad structural diversity and a wide range of binding affinities. When applied to 58,000 chemicals identified by Walker et al. as candidates for endocrine disruption screening, some 9100 chemicals were predicted to bind to ER. Of these, only 3600 were expected to bind to ER at RBA values up to 100,000-fold less than that of 17beta-estradiol. The method ruled out 83% of the chemicals as non-binders with a very low rate of false negatives. We believe that the same integrated scheme will be equally applicable to endpoints of other endocrine disrupting mechanisms, e.g. androgen receptor binding.

Biological Assay↗

Immunolocalization and possible effect of a moth allatotropin-like substance in a fly, Phormia regina (Diptera: Calliphoridae).

Insect allatotropin upregulates the biosynthesis of juvenile hormones by the corpus allatum. We raised two rabbit antisera against the allatotropin of Manduca sexta (Mas AT) using a synthetic, multiple-antigenic-peptide that contains a branching heptalysine core and eight Mas AT molecules. Both antisera recognized specifically the same neurons in the larval brain, frontal ganglion and terminal abdominal ganglion of M. sexta as previously reported by others. Immunoassay showed reactivity specific to the Mas AT. Very low or nearly no cross-reactivity was found for two Mas AT-like peptides, a myotropin from Locusta migratoria and a Mas AT-like peptide deduced from the DNA sequence of Aedes aegypti, respectively. Immunopositive neurons also were identified in adult Phormia regina, Dacus dorsalis, Oncopeltus fasciatus, and Mythimna loreyi, and in larval M. loreyi, Bombyx mori, and Andraca bipunctata. At 20 pmol per 25 µl incubation medium (i.e. 8x10(-7) M), synthetic Mas AT significantly stimulated in vitro juvenile hormone biosynthesis by the corpus allatum of adult, sugar-fed females of P. regina to 2.64-fold that of controls. Thus, this study provides the first demonstration that at the higher end of the physiological concentration range, the Mas AT has allatotropic effect in vitro to CA of non-lepidopterans. However, in vivo functions of Mas AT and/or Mas AT-like peptide in P. regina remain to be defined.

Journal Article↗

Preparation and blood compatibility of polysiloxane/liquid-crystal composite membranes.

Polysiloxane/liquid crystal composite membrane was first suggested to be used as biomaterials. In this work, the polydimethyl-methylhydrosiloxane and polydimethyl-methylethylenesilosiane, as a substrate, were blended with cholesteryl oleyl carbonate (COC) in tetrahydrofuran, and then crosslinked into membranes on glass plates by means of the platinum catalyst at 110 degrees C for 20 min. The effects of the liquid-crystal content in composite membranes on the formation of liquid-crystal phase were verified by the observation of optical polarization microscopy. The relationship between the morphology of the composite membranes and blood compatibility was identified by the dynamic blood-clotting tests, haemolysis ratio measurement, platelet adhesion and SEM observation. The results show that the blood-compatibility of composite membranes with the concentration of liquid crystal 20, 30% (wt) is more excellent than that of other composite membranes.

Biocompatible Materials↗

Predicted changes in pre-mRNA secondary structure vary in their association with exon skipping for mutations in exons 2, 4, and 8 of the Hprt gene and exon 51 of the fibrillin gene.

Exon skipping that accompanies exonic mutation might be caused by an effect of the mutation on pre-mRNA secondary structure. Previous attempts to associate predicted secondary structure of pre-mRNA with exon skipping have been hindered by either a small number of available mutations, sub-optimal structures, or weak effects on exon skipping. This report identifies more extensive sets of mutations from the human and hamster Hprt gene whose association with exon skipping is clear. Optimal secondary structures of the wild-type and mutant pre-mRNA surrounding each exon were predicted by energy minimization and were compared by energy dot plots. A significant association was found between the occurrence of exon skipping and the disruption of a stem containing the acceptor site consensus sequences of exon 8 of the human Hprt gene. However, no change in secondary structure was associated with skipping of exon 4 of the hamster Hprt gene. Using updated energy parameters we found a different structure than that previously reported for exon 2 of the hamster Hprt gene. In contrast to the previously reported structure, no significant association was found between predicted structural changes and skipping of exon 2. For all three Hprt exons studied, there was a significantly greater number of deoxythymidine substitutions among mutations accompanied by exon skipping than among mutations without exon skipping. For exon 8, deoxythymidine substitution was also associated with structural changes in the stem containing the acceptor site consensus sequences. For exon 51 of the human fibrillin gene, structural differences from wild type were predicted for all four mutations accompanied by exon skipping that were not were predicted for a single mutation without exon skipping. Our results suggest that both primary and secondary pre-mRNA structure contribute to definition of Hprt exons, which may involve exonic splicing enhancers.

Animals↗

[Clinical study of prophylactic cranial irradiation for small-cell lung cancer].

OBJECTIVE: To study the influence of prophylactic cranial irradiation (PCI) on survival and brain metastases in patients with limited small-cell lung cancer (SCLC). METHODS: Fiftyone patients with limited SCLC under complete remission after chemoradiotherapy were randomly divided into prophylactic cranial irradiation (PCI) group (n = 26) and control group (n = 25). Patients in PCI group received irradiation at a dose of 25.2-30.6 Gy. Survival rates were analyzed and compared by life table and Long-Rank, incidence of cranial metastases by chi 2 test. RESULTS: The clinical features of patients such as age, sex, effect of treatment before PCI were similar between the two groups. The incidence of cranial metastases was 3.8% in PCI group in contrast to 28% in the control group (P < 0.05). The 1, 2, 3-year survival rate was 84.6%, 73.1%, 42.3% respectively in PCI group and 72%, 40%, 32% respectively in the control group. The differences between the two groups of petients were statistically insignificant. No serious sequela was observed in patients receiving PCI. CONCLUSION: PCI decreases the incidence of cranial metastases for patients with limited SCLC following complete response to chemoradiotherapy, but it does not improve survival.

Adult↗

[The expression of interleukin-6 mRNA and autosecretion in human leukemic cells].

OBJECTIVE: To make a comprehensive and systematic study on the constructive expression of IL-6 mRNA and IL-6 autosecretion in human leukemic cells and discuss the effect of IL-6 autosecretion on the specific binding of IL-6-PE40 fusion protein to targeted leukemic cells. METHODS: Semi-quantitative RT-PCR, sequencing and ELISA were used to detect the constructive expression of IL-6 mRNA and autosecretion level of IL-6 protein in human leukemic cell lines, such as U937, HL60, KG1, TF1, K562, HuT28, CEM and Raji. RESULTS: The relative expression level of IL-6 mRNA in myelocytic, monocytic and erythrocytic leukemic cell lines including HL60, U937, KG1 and TF1 and lymphoblastic leukemic cell lines such as CEM, HuT28 and Raji is very weak, ranging from 0.03 to 0.07. However, K562, an chronic myelocytic leukemic cell line, had the highest level 1.25 among the 8 leukemic cell lines and the level was also higher than that of the positive control U266 multiple myeloma cell line. Based on ELISA assay of IL-6, there were remarkable differences between the 8 leukemic cell lines, their secretion of IL-6 could be divided into 3 levels, i.e. high, moderate and low secretion type. CONCLUSION: These observations imply that the intrinsic expression and secretion of IL-6 differ obviously among different leukemic cell lines. Autocrine IL-6 may prevent IL-6-PE40 fusion protein from specific binding to targeted leukemic cells and consequently affect its specific killing toxicity.

Cell Line, Tumor↗

Diversity analysis of 14 156 molecules tested by the National Cancer Institute for anti-HIV activity using the quantitative structure-activity relational expert system MCASE.

Using the MCASE program, a procedure to analyze the diversity of the large amount of available HIV-1 antiviral data was proposed. A subset of 1 819 chemicals was logically selected from the original 14 156 chemicals tested by NCI. This subset of chemicals was shown to contain most of the structural and the functional information of the original database. A full analysis of the 1 819 chemicals by the MCASE program produced a correlation between chemical structures and HIV antiviral activity. In our model, 74 fragments were identified as being responsible for all the chemical's HIV antiviral activity. These fragments may be related to different inhibiting mechanisms, some known and some probably still unknown. The expert system resulting from this analysis can be used to predict the activity of new chemicals and to design new agents that can target multiple enzymes. This was shown to be the case by using the model to predict the activity of 10 diverse chemicals whose activities were not known at the time of model development. Of these, 8 were predicted in agreement with experimental observations. As far as we can tell, this is probably the first project ever to attempt to create a quantitative model of activity for such a massive database of diverse chemicals.

Anti-HIV Agents↗

Tissue distribution of recombinant human tumor necrosis factor alpha derivative in mice.

AIM: To study the tissue distribution and its mechanism of a new recombinant tumor necrosis factor alpha derivative (rhTNF alpha Da) in mice. METHODS: 125I-rhTNF alpha Da was prepared by Iodogen method. Tissue distribution of 125I-rhTNF alpha Da in mice was studied by determining radioactivity of tetrachloroacetic acid (TCA)- precipitable fraction in tissues. The isolated heart-lung perfusion study using 125I-rhTNF alpha Da perfusate was carried out to study the distribution characteristics of 125I-rhTNF alpha Da in lung. RESULTS: Except for thyroid, AUC of the TCA-precipitable 125I-rhTNF alpha Da in tissues was highest in lung, which was 12.2-fold of that in serum, while concentrations in other tissues were all lower than that in serum. Perfusion study in vitro revealed that the concentration of radio-labeled peptide in lung was higher than that in perfusate. On the contrary, level in heart was much lower than that in perfusate. The overall distribution of 125I-rhTNF alpha Da in lungs showed rapidly equilibratory, dose-dependent, saturable, competitive, and highly affinitive, with Kd 47.6 pmol.L-1 and Bmax 348 fmol.g-1 (lung tissue). CONCLUSION: The specific distribution of rhTNF alpha Da in lungs was its distinctive characteristics.

Animals↗

MODULATION OF NEGATIVE WORK OUTPUT FROM A STEERING MUSCLE OF THE BLOWFLY CALLIPHORA VICINA

Of the 17 muscles responsible for flight control in flies, only the first basalar muscle (b1) is known to fire an action potential each and every wing beat at a precise phase of the wing-beat period. The phase of action potentials in the b1 is shifted during turns, implicating the b1 in the control of aerodynamic yaw torque. We used the work loop technique to quantify the effects of phase modulation on the mechanical output of the b1 of the blowfly Calliphora vicina. During cyclic length oscillations at 10 and 50 Hz, the magnitude of positive work output by the b1 was similar to that measured previously from other insect muscles. However, when tested at wing-beat frequency (150 Hz), the net work performed in each cycle was negative. The twitch kinetics of the b1 suggest that negative work output reflects intrinsic specializations of the b1 muscle. Our results suggest that, in addition to a possible role as a passive elastic element, the phase-sensitivity of its mechanical properties may endow the b1 with the capacity to modulate wing-beat kinematics during turning maneuvers.

Journal Article↗

Developmental incompatibility between cell nucleus and cytoplasm as revealed by nuclear transplantation experiments in teleost of different families and orders.

Teleosts from different families and orders were used as materials for nuclear transplantation experiments. (1) The nuclei of goldfish (Carassius auratus, family Cyprinidae, order Cypriniformes) were transplanted into the enucleated egg cytoplasm of loach (Paramisgurnus dabryanus, family Cobitidae, order Cypriniformes) and vice-versa. (2) The nuclei of Tilapia (oreochromis nilotica, order Perciformes) were transplanted into the enucleated egg cytoplasm of goldfish (Carassius auratus, order Cypriniformes). The chromosome number of the nucleus donor fish is different from that of the cytoplasmic recipient fish in each of the two combinations. In the first case, only a few early nucleo-cytoplasmic hybrid (NCH) larval fish were obtained in each combination. In second case, even though a high percentage of NCH blastulas were also obtained, the majority of them died at the same developmental stage, except a few which survived until early gastrula stage. The examination of the metaphase chromosome figures of the NCH blastulas or embryos obtained in all three combinations indicated that they were of nucleus-donor type. The developmental rates of all the NCH eggs were similar to those of cytoplasmic-recipient type. Scanning electronmicroscopy examination showed that the morphology of NCH blastula cells, which were obtained from the combination of Tilapia nucleus and goldfish cytoplasm, manifested obviously abnormal features and the cells were arrested at different stages of cell disintegration. Two-dimension polyacrylamide gel electrophoretograms of the homogenates of Tilapia, goldfish and their NCH blastula cells showed that the protein synthetic pattern of NCH blastula was similar to that of Tilapia nucleus type. The results of experiments which failed to obtain NCH adult fish in all three combinations can be explained as a result of developmental incompatibility between the donor nucleus and the enucleated recipient egg cytoplasm, which were from distantly related fish species. And the chromosome numbers of all the component fish of the three combinations which were examined in the experiment and shown to be quite different from each other in the tested fish, should not be overlooked as one of the essential factors causing the developmental incompatibility in NCH fish in this experiment.

Animals↗

Expression of organ-specific antigens on capillary endothelial cells.

Our central thesis is that the endothelial cells which line capillaries of various organs are not all alike. Using monoclonal and conventional antibodies we demonstrate that capillary endothelial cells express on their cell surface an array of antigens that manifest organ selectivity. Brain-derived endothelial cells possess brain-associated antigens, ovary-derived endothelial cells share antigenic markers with other ovarian cells, and lung-derived endothelium possesses antigens that are primarily expressed on cells of the lung. Our experiments lead us to suggest that organ-associated determinants on the endothelial cell surface may play a role in the selective adhesion of tumor cells during metastasis, in site-limited vascular pathology, and in the regionally limited release of angiogenesis-induced factors.

Animals↗

A teratocarcinoma-derived endoderm stem cell line (1H5) that can differentiate into extra-embryonic endoderm cell types.

We investigated the ability of the teratocarcinoma-derived, epithelial-type cell line 1H5 to differentiate into either of the two pathways to primary endoderm, and tested the hypothesis that 1H5 represents a state similar to primitive endoderm in the late 4th-day blastocyst. Like other endodermal cell types, 1H5 cells mixed with embryonal-carcinoma cells sort out into "embryoid bodies" or structures that resemble 4th-day mouse embryos. The epithelial line conforms morphologically and biochemically to the few known characteristics typical of primitive endoderm. The present study demonstrates that the formation in vitro of overt visceral endoderm is readily achieved. The spontaneous arrangement of the cells into a cystic form is followed by the appearance of several markers of visceral endoderm, most notably alphafetoprotein, which is detected when 1H5 cells are cultured either in the presence of retinoic acid or when the cells interact with embryonal-carcinoma cells in a specific spatial arrangement after sorting out. However, some less specific properties of visceral endoderm are not expressed. Although 1H5 differentiates histologically into parietal-like endoderm in the tumor form, parietal cells cannot yet be identified with certainty in vitro because of the paucity of parietal-specific markers. The 1H5 cell line could provide a useful system for studying the characteristics and mechanisms underlying visceral-endoderm differentiation in vitro, since it has the distinct advantage that homogeneous cultures are produced, in contrast to other teratocarcinoma cell lines such as F9 which differentiate into a mixture of cell types.

Animals↗

Monoclonal antibody against angiotensin-converting enzyme: its use as a marker for murine, bovine, and human endothelial cells.

A monoclonal antibody has been prepared against rat angiotensin-converting enzyme (ACE). By selection for antibody binding to endothelial cells of bovine rather than rat origin we have obtained a reagent that has broad cross-species binding properties and that can at the same time serve as a useful marker for the surface of endothelial cells. The IgM-producing clone that we have established, alpha-ACE 3.1.1, has been grown in ascites form to yield ascites fluid that binds selectively to immobilized ACE at a greater than 1:10,000 dilution. By use of enzyme-linked immunosorbent assays, immunofluorescence histology, and flow cytometry, we have demonstrated the presence of ACE on endothelial cells of murine, bovine, and human origin. By means of a fluorescence-activated cell sorter (FACS-IV) we have been able to selectively isolate viable endothelial cells from a mixture of endothelial cells and fibroblasts. We believe the antibody will be useful not only for the selection and in vitro cultivation of endothelial cells but also as a tool for the identification and pharmacological study of ACE.

Animals↗